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Abstract

Background

Body Mass Index (BMI) is widely used to assess the impact of obesity on cardiometabolic
risk in children but it does not always relate to central obesity and varies with
growth and maturation. Waist-to-Height Ratio (WHtR) is a relatively constant anthropometric
index of abdominal obesity across different age, sex or racial groups. However, information
is scant on the utility of WHtR in assessing the status of abdominal obesity and related
cardiometabolic risk profile among normal weight and overweight/obese children, categorized
according to the accepted BMI threshold values.

Methods

Cross-sectional cardiometabolic risk factor variables on 3091 black and white children
(56% white, 50% male), 4-18 years of age were used. Based on the age-, race- and sex-specific
percentiles of BMI, the children were classified as normal weight (5th - 85th percentiles)
and overweight/obese (≥ 85th percentile). The risk profiles of each group based on
the WHtR (<0.5, no central obesity versus ≥ 0.5, central obesity) were compared.

Results

9.2% of the children in the normal weight group were centrally obese (WHtR ≥0.5) and
19.8% among the overweight/obese were not (WHtR < 0.5). On multivariate analysis the
normal weight centrally obese children were 1.66, 2.01, 1.47 and 2.05 times more likely
to have significant adverse levels of LDL cholesterol, HDL cholesterol, triglycerides
and insulin, respectively. In addition to having a higher prevalence of parental history
of type 2 diabetes mellitus, the normal weight central obesity group showed a significantly
higher prevalence of metabolic syndrome (p < 0.0001). In the overweight/obese group,
those without central obesity were 0.53 and 0.27 times less likely to have significant
adverse levels of HDL cholesterol and HOMA-IR, respectively (p < 0.05), as compared
to those with central obesity. These overweight/obese children without central obesity
also showed significantly lower prevalence of parental history of hypertension (p
= 0.002), type 2 diabetes mellitus (p = 0.03) and metabolic syndrome (p < 0.0001).

Conclusion

WHtR not only detects central obesity and related adverse cardiometabolic risk among
normal weight children, but also identifies those without such conditions among the
overweight/obese children, which has implications for pediatric primary care practice.

Background

Childhood obesity is reaching epidemic proportions worldwide [1]. Although childhood obesity is a well recognized risk factor for developing cardiovascular
disease and type 2 diabetes mellitus in adulthood, excess central (intra-abdominal)
body fat distribution may be more related to these diseases than peripheral distribution
[2]. Body Mass Index (BMI) is widely used as a measure to evaluate the impact of obesity
on cardiovascular and metabolic risk factors, both in children and adults. However,
in children, the BMI measures have to be expressed as z scores or percentiles relative to age and sex as BMI is strongly related to growth
and maturation [3]. Moreover, BMI does not always relate to central obesity [4] and it cannot differentiate muscle mass from bone and fat mass [5]. Waist-to-Height Ratio (WHtR) has been proposed as an easily measurable anthropometric
index for detection of central obesity and to assess associations between cardiometabolic
risk factor variables and central intra-abdominal obesity [6-10]. Studies in adults have shown that it is possible to identify not only those with
normal weight having an adverse cardiometabolic risk profile but also those with overweight/obese
condition having normal metabolic risk profile [2,5,11]. Although studies relating BMI and WHtR to cardiovascular (CV) disease risk factors
in children and adolescents are emerging [6,12-17], information is scant on the utility of WHtR in assessing the status of abdominal
obesity and related cardiometabolic risk profile among normal weight and overweight/obese
children. The objective of this current study was to examine this aspect in children
enrolled in the Bogalusa Heart Study, a biracial (black-white) community-based study
of the natural history of CV disease since childhood [18].

Methods

Study population

The present study sample was derived from 3238 children, 4-18 years of age (mean age
10.98 years, 50% male, 56% white). After excluding those with age-, race- and sex-specific
BMI less than the 5th percentile (n = 147), the subjects were divided into two groups: the normal weight
group (n = 2581), with BMI between the 5th and the 85th percentiles; the overweight/obese group (n = 510), with BMI ≥ 85th percentile. Using the previously recommended cut-point [6,8,14], children in each group were sub-divided based on their WHtR: centrally obese (WHtR
≥ 0.5) or non-centrally obese (WHtR < 0.5). The protocols of this study were approved
by the Institutional Review Board of the Tulane University Health Sciences Center.
Informed consent was obtained from all the participants, for those under 18 years
of age, consent of a parent/guardian was obtained.

General examination

Standardized protocols were used by trained examiners [19]. The subjects were instructed to fast overnight before screening. Anthropometric
and blood pressure measurements were made in replicate, and the mean values were used.
The BMI was calculated as the weight in kilograms divided by the square of height
in meters. Waist circumference was measured midway between the lowest border of rib
cage and the upper border of iliac crest while the child was standing. Blood pressure
measurements were obtained using a mercury sphygmomanometer, on the right arm of the
participants who were in a relaxed sitting position, by two trained observers, each
recording three measurements. The first and the fourth Korotkoff phases were recorded
for systolic and diastolic blood pressures respectively, and average levels were used
for analysis.

Laboratory Analyses

Serum cholesterol and triglyceride levels were assayed using enzymatic procedures
(Abbott VP, North Chicago, Illinois) [20,21]. The levels of lipoprotein cholesterol were analyzed by a combination of heparin-calcium
precipitation and agar-agarose gel electrophoresis procedures [22]. Plasma insulin measurements were obtained with the use of a commercial radio-immunoassay
kit (Phadebas Insulin Kit; Pharmacia Diagnostics, Piscataway, NJ). Glucose was measured
as part of a multiple chemistry profile (SMA 20) by a glucose oxidase method. The
laboratory is monitored for precision and accuracy of lipid measurements by the Lipid
Standardization and Surveillance Program of the Centers for Disease Control and Prevention
(Atlanta, GA). Insulin resistance status was assessed as homeostasis model assessment
of insulin resistance (HOMA-IR) according to the formula described [23]: insulin (μU/mL) × glucose (mmol/L)/22.5.

Statistical Analysis

All statistical analyses were performed using Statistical Analysis Systems, version
9.1 (SAS Institute, Cary, North Carolina). Continuous variables were tested for normality
using the Kolmogorov-Smirnov test. The values of insulin and HOMA-IR were log transformed
to improve the normality of distribution. The differences in the mean values (mean
± standard error) of the cardiometabolic risk factor variables between the sub-groups
were tested separately for each of the two groups (normal weight and overweight/obese)
by analysis of covariance, adjusting for age, race and sex wherever necessary. In
multivariate analyses, independent associations between the cardiometabolic risk factor
variables and central obesity were examined for both groups using separate multivariate
logistic regression analysis models, taking the presence or absence of central obesity
(yes/no) as the dependent variable. Adverse levels were defined as age-, race- and
sex- specific top tertiles of each cardiometabolic risk variable (except for HDL cholesterol)
and the lower two tertiles were used as the reference group; bottom tertile versus
the rest for HDL cholesterol. Categorical variables and prevalence rates were compared
using χ2 tests. With respect to metabolic syndrome, although there is a plethora of definitions
used in studies of children, we used the one outlined by Cook et al [24].

Results

Figure 1 illustrates the prevalence of central obesity among normal weight and overweight/obese
groups. Based on the WHtR (<0.5 vs. ≥ 0.5), 9.2% of children in the normal weight
group had central obesity (n = 238), and 19.8% of the overweight/obese group did not
(n = 101).

The results of the multivariate logistic regression analysis are presented in Table
2. After adjusting for age, race and sex, the centrally obese normal weight group was
1.66, 1.47, and 2.05 times more likely than the non-centrally obese normal weight
(reference group) to have significantly elevated levels of LDL cholesterol, triglycerides
and insulin, respectively, and 2.01 times more likely to have significantly lower
levels of HDL cholesterol. On the other hand, the odds of having adverse levels of
HDL cholesterol and HOMA-IR were 0.53 and 0.27 times lower, respectively, in the non-centrally
obese overweight/obese group versus the reference centrally obese overweight/obese
group.

Figure 2. demonstrates the prevalence of metabolic syndrome according to the WHtR groups in
the normal weight and the overweight/obese children. As expected, 5.88% of the centrally
obese normal weight subjects had metabolic syndrome as compared to only 0.26% of the
normal weight without central obesity (p < 0.0001). Similarly, none of the overweight/obese
children without central obesity showed the presence of metabolic syndrome whereas
the prevalence in the centrally obese overweight/obese was as high as 21.27% (p <
0.0001).

Figure 2.Prevalence of Metabolic Syndrome in Normal Weight and Overweight/Obese Children According
to Waist-to-Height Ratio: The Bogalusa Heart Study.

As listed in Table 3., the prevalence of parental history of type 2 diabetes mellitus was significantly
higher in individuals in the normal weight group having central obesity (11.71% vs.
6.63%, p = 0.007). The overweight/obese children without central obesity had a significantly
lower prevalence with respect to parental history of hypertension (23.86% vs. 41.31%,
p = 0.002) and type 2 diabetes mellitus (8.24% vs. 17.66%, p = 0.03) as compared to
those with central obesity.

Table 3. Prevalence of parental history of hypertension, cardiovascular disease and type 2
diabetes in normal weight and overweight/obese children by waist-to-height ratio:
The Bogalusa Heart Study.

Discussion

In this present cross-sectional, community-based study we used WHtR as a simple anthropometric
index to identify the status of central (visceral) obesity and cardiometabolic risk
factor profiles in groups of normal weight and overweight/obese children, selected
based on traditional BMI criteria. Earlier studies in adults and children have supported
the practicality of this convenient anthropometric index [6,8,10,15-17]. We found that while the normal weight children with central obesity had adverse
levels of cardiometabolic risk factor variables as compared to those without central
obesity, the overweight/obese without central obesity had significantly lower levels
in relation to those with central obesity. These observations in children are in accordance
with the emerging concepts that recognize subsets of obesity and support the existence
of metabolically obese normal weight, and metabolically benign obesity phenotypes
in adults [2,10,11,25]. These findings support the pathophysiologic role of intra-abdominal body fat distribution
in determining interrelated cardiometabolic risk variables collectively recognized
as metabolic syndrome [26-29]. It is now well recognized that central adiposity acts as a complex and highly active
endocrine organ resulting in a variety of hormones and cytokines (tumor necrosis factor-α,
interleukin-6 etc.), which in turn can play an important role in the dysregulation
of inflammatory, metabolic and hemodynamic processes in the body through various mechanisms
including hepatic lipogenesis and hepatic insulin resistance, release of free fatty
acids from adipocytes, macrophage infiltration into the adipose tissue, adipose renin-angiotensin-aldosterone
system and sympathetic nervous system activation and ectopic lipid storage [11,30,31].

Central obesity status regardless of normal weight or overweight/obesity condition
in children is related to parental history of hypertension and type 2 diabetes, underscoring
the familial nature of the relationship shown earlier in the Bogalusa Heart Study
cohort [32,33]. Even though the overweight/obese without central obesity had a lower prevalence
of parental history of CV disease the difference did not reach the level of significance.
This may be explained by the fact that our study subjects are children and the age
of onset of CV disease is higher than that of type 2 diabetes mellitus.

We believe that the above mentioned observations have important public health implications.
The traditional cut-offs for BMI may underestimate the cardiometabolic risk in the
normal weight and overestimate the same in the overweight/obese children while WHtR
may be more sensitive in identifying the children at risk, especially at a population
level, and provide a better estimate of the overall risk. As normal weight children
may have already developed central obesity, health awareness efforts must include
such children and advocate lifestyle changes, which may be easier to achieve in this
group, before they develop overt obesity and its complications.

This community-based study had certain limitations in that it lacked direct assessments
of pubertal status, body fat mass and distribution and in vivo insulin action. Instead,
we used well-established surrogate measures that are simple and appropriate at the
population level. Furthermore, this study being observational and cross-sectional
in nature, could not address the issue of causality.

Conclusion

The findings of the present study emphasize the utility of WHtR not only in detecting
central intra-abdominal obesity and related cardiometabolic risk among normal weight
children, but also in identifying those without central obesity and a healthy risk
factor profiles among the overweight/obese children. Thus, WHtR has a potential for
wider use as a simple measure to assess cardiometabolic risk in pediatric primary
care practice.

Decleration of Competing interests

The authors declare that they have no competing interests.

Authors' contributions

JSM made substantial contributions to the study design and acquisition of the data,
performed statistical analysis, drafted the manuscript and made revisions. SRS participated
in designing the study and revised the manuscript for intellectual content. PM assisted
in statistical analysis and acquisition of the data. CF made contributions to the
study design. WC made revisions to the manuscript and overlooked statistical analysis.
JX carried out the laboratory analyses. GSB conceived of the study, revised the manuscript
for intellectual content and gave final approval of the version to be submitted. All
authors read and approved the final manuscript.

Acknowledgements

The Bogalusa Heart Study is a joint effort of many investigators and staff members,
whose contributions are gratefully acknowledged. We especially thank the study participants,
without whom this study would not be possible.

Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle B, Mietus-Snyder ML: Progress and challenges in metabolic syndrome in children and adolescents: a scientific
statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity
in the Young Committee of the Council on Cardiovascular Disease in the Young; Council
on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism.